van Rij Ronald P, van Praag Rieneke M E, Prins Jan M, Rientsma Ronald, Jurriaans Suzanne, Lange Joep M A, Schuitemaker Hanneke
Department of Clinical Viro Immunology, CLB/Sanquin and Landsteiner Laboratory of the Academic Medical Center, Amsterdam, The Netherlands.
Antivir Ther. 2002 Mar;7(1):37-41.
During sustained suppression of plasma viraemia using a standard triple-drug regimen, replication-competent HIV-1 can still be recovered from resting memory CD4 T cells. In an attempt to accelerate the clearance of this pool of infected CD4 T cells, eight antiretroviral therapy-naive HIV-1-infected patients were treated with a five-drug regimen. While plasma HIV-1 RNA levels generally remained below the level of detection (< 5 copies/ml), replication competent HIV-1 was isolated from HLA-DR- CD4 T cells from all patients on multiple occasions throughout treatment. Decay slopes of infected CD4 T cells ranged from -0.061/week (half-life=2.6 months) to +0.003/week (half-life = infinite). Virus was still detectable at the last time point analysed (80-173 weeks) in all patients. Although more intensive treatment results in improved suppression of plasma viraemia compared with standard drug regimens, it does not result in clearance of the viral reservoir in this timeframe. Strategies other than treatment with a combination of five of the currently available drugs need to be pursued in order to achieve eradication of HIV-1 from this cellular reservoir.
在使用标准三联药物疗法持续抑制血浆病毒血症期间,仍可从静息记忆CD4 T细胞中分离出具有复制能力的HIV-1。为了加速清除这群被感染的CD4 T细胞,对8例未接受过抗逆转录病毒治疗的HIV-1感染者采用五联药物疗法进行治疗。虽然血浆HIV-1 RNA水平通常保持在检测下限以下(<5拷贝/毫升),但在整个治疗过程中,多次从所有患者的HLA-DR-CD4 T细胞中分离出具有复制能力的HIV-1。被感染CD4 T细胞的衰减斜率范围为-0.061/周(半衰期=2.6个月)至+0.003/周(半衰期=无限)。在最后一个分析时间点(80-173周),所有患者体内仍可检测到病毒。尽管与标准药物疗法相比,更强化的治疗能更好地抑制血浆病毒血症,但在这个时间段内并不能清除病毒储存库。为了从这个细胞储存库中根除HIV-1,需要探索目前可用的五种药物联合治疗以外的策略。